1x9n

Disease
Known disease associated with this structure: DNA ligase I deficiency OMIM:[126391]

The expression of DNA ligase I has been directly linked to cancer in humans. The enzyme is found most in proliferating cells and much less often in nondividing cells. In particular, in malignant tumors, the DNA ligase I enzyme was expressed much more compared to the DNA ligase I enzyme in normal tissues and their peripheral lymphocytes. Further experimentation showed that tumor cell growth rate was successfully decreased when antisense oligonucleotides targeting the mRNA of DNA ligase I were present. This suggests that DNA ligase I could be a good target for new anticancer studies.

''Elevated expression of DNA ligase I in human cancers., Sun DY, Urrabaz R, Nguyen M, Marty J, Stringer S, Cruz E, Medina-Gundrum L, Weitman S., Clinical Cancer Research. 2001; 7(12):4143-4148.''

A specific point mutation (46BR in the mouse Lig1 gene) in DNA ligase I has also been linked as a cause for genome instability and cancer in humans. One possible reason for this is the accumulation of DNA fragments that are no longer ligated by the mutant DNA ligase I enzyme.

''Replication failure, genome instability, and increased cancer susceptibility in mice with a point mutation in the DNA ligase I gene., Harrison C, Ketchen AM, Redhead NJ, O'Sullivan MJ, Melton DW., Cancer Research. 2002; 62(14):4065-4074.''

About this Structure
1X9N is a 4 chains structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

3D structures of DNA ligase
DNA ligase

Reference
Page seeded by OCA on Tue Feb 17 05:54:17 2009


 * Sun DY, Urrabaz R, Nguyen M, Marty J, Stringer S, Cruz E, Medina-Gundrum L, Weitman S. 2001. Elevated expression of DNA ligase I in human cancers. Clinical Cancer Research 7(12):4143-4148.


 * Harrison C, Ketchen AM, Redhead NJ, O'Sullivan MJ, Melton DW. 2002. Replication failure, genome instability, and increased cancer susceptibility in mice with a point mutation in the DNA ligase I gene. Cancer Research 62(14):4065-4074.